With age, subcutaneous muscles lengthen and give a sagging appearance to the skin because underlying muscle is looser. Current treatments of placid skin and muscles from aging typically involve plastic surgery. The plastic surgeon cuts the skin and muscle and then pulls it taut, reducing some of the tissue and discarding it, then suturing it so that the facial, chest and/or buttocks muscles remain tight.
The external appearance of aging individuals is particularly affected by subcutaneous changes in skeletal muscle tissue. When muscles are at rest, a certain amount of tautness usually remains. The residual degree of contraction in skeletal muscles is called muscle tone. In aging individuals, the degree of contraction relaxes, and is particularly obvious in the face.
In order for a muscle to contract, a message is sent from the brain to the spinal cord, and then from the spinal cord to the skeletal muscles. This is accomplished by an action potential which travels down the axon of the nerve. The nerve ends at an area called the synaptic knob, and this action potential causes the synaptic knob to release small diffusible chemical neurotransmitters into the synaptic cleft. The synaptic knob is rich in tiny vesicles containing neurotransmitters, and these vesicles are rich in acetylcholine in knobs innervating muscles. Acetylcholine is released into the synaptic cleft, and then meets the muscle at an invagination called the synaptic gutter. This acetylcholine then finds receptors on the muscle surface, which causes the muscle to become permeable to sodium ions, which result in membrane potential increases in the local area of the end plate, about 75 millivolts, creating a local potential called the end plate potential. This causes the muscle to contract.
Once this contraction takes place, the remaining acetylcholine in the cleft is destroyed by an enzyme called cholinesterase. The choline is reabsorbed by the pre-synaptic knob to be used again to synthesize acetylcholine. Thus, it is at this neuromuscular junction where acetylcholine causes its effect. The synaptic knobs have the capability of continually synthesizing new transmitter substance. This occurs mainly in the cytoplasm of the synaptic knobs, and then it is absorbed into tiny vesicles and stored as needed.
It can be seen that neurotransmission at neuromuscular junctions is a complicated process affected by many factors including the biosynthesis of the neurotransmitter, storage of the neurotransmitter, release of the neurotransmitter, interaction of the neurotransmitter with receptors on effector cells, and termination of neurotransmitter activity by reuptake and/or metabolic processes.
The process is further complicated by the interactions among neurotramsmitters in the sympathetic and parasympathetic nervous systems. As described above, cholinergic neurons act at the myoneural junction and cause skeletal muscle contraction through the action of chemical mediators such as acetylcholine at synapses in the parasympathetic nervous system. In the sympathetic (autonomic) nervous system, adrenergic neurons employ other neurotransmitters at smooth muscle junctions, e.g., norepinephrine, epinephrine, dopamine, and serotonin. Norepinephrine is a mediator of activity at most postganglionic sympathetic endings in the autonomic nervous system. Neurotransmitters of the adrenergic neurons enhance neurotransmitters at the myoneural junction, e.g., acetylcholine release. Thus, epinephrine, an adrenergic catecholamine, can affect muscle contraction by enhancing the release and effects of acetylcholine at the myoneural junction.
The principal catecholamines found in the body, norephinephrine, epinephrine, and dopamine, are formed by hydroxylation and decarboxylation of the amino acids phenylalanine and tyrosine. Tyrosine is transported into adrenergic nerve endings by a concentrating mechanism. It is converted to dopa by hydroxylation and then decarboxylated to dopamine (3,4-dihydroxyphenylethylamine) in the cytoplasm of the neurons by tyrosine hydroxylase and dopa decarboxylase, respectively. The dopamine then enters the granulated vesicles from which it is converted to norepinephrine (noradrenaline) by dopamine .beta.-hydroxylase. L-dopa is the isomer involved, and it is the Lisomer of norepinephrine that is produced. The rate-limiting step in synthesis is the conversion of tyrosine to dopa. Tyrosine hydroxylase which catalyzes this step is subject to feedback inhibition by dopamine and norepinephrine, thus providing internal control of the synthetic process. The co-factor for tyrosine hydroxylase is tetrahydrobiopterine, which is converted to dihydrobiopterine when tyrosine is converted to dopa.
Norepinepherine is synthesized in nerve endings but can also be resorbed by nerve endings after systemic secretion. This active uptake mechanism is characteristic of adrenergic neurons. It is also known that circulating norepinephrine and epinephrine (adrenaline, methylated norepinephrine) within the body are incorporated in small amounts by adrenergic neurons in the autonomic nervous system. Thus, adrenergic neurons differ from cholenergic neurons in the ability to uptake a complete molecule. Acetylcholine is not taken up to any appreciable degree, but the choline that is formed by the action of acetyl cholinesterase is taken up and recycled.
The aging process results in damage to presynaptic knobs, and therefore fewer neurotransmitters become available to a muscle for contraction. Receptor sites on muscle also deteriorate, and are unable to respond to the levels of acetylcholine present. Muscle tone maintained by nerve fibers releasing acetylcholine to small areas of muscle decreases, so that an appearance of sagging is observed.
In addition to changes in subcutaneous muscle tissue, the overlying epidermis thins and the skin appendages atrophy with age. Hair becomes sparse and sebaceous secretions decrease, with consequent susceptibility to dryness, chapping, and fissuring. The dermis diminishes with loss of elastic and collagen fibers. Typical treatment of sun-damaged and aged skin consists primarily of applications of various creams, lotions and gels to add moisture to the skin, as well as various acid peels to retexture the skin.
Cell age is due in part to free radical damage, which takes place mostly within the cell membrane. The cell membrane is most susceptible to attack by free radicals because of its dense molecular structure largely comprising lipids and lipoproteins, which are easily oxidized by reactive oxygen species. In the epidermis, reactive oxygen species, such as singlet oxygen, the superoxide anion, and hydroxyl radicals, and other free radicals are generated in normal metabolism, as well as through ultraviolet sun exposure, other forms of radiation, other environmental factors such as pollution or exposure to chemicals in the home or workplace, and the like. In addition, free radicals can activate chemical mediators of inflammation, particularly where arachadonic acid is released, which is then oxidized via two predominant pathways to produce either prostaglandins or leukotrines.
The body contains an endogenous antioxidant defense system made up of antioxidants such as vitamin E, vitamin C, superoxide dismutase, and glutathione. When metabolism increases or the body is subjected to other stress such as extreme exercise, radiation (ionizing and non-ionizing), or chemicals, the endogenous antioxidant systems are overwhelmed, and free radical damage takes place. Over the years, the cell membrane continually receives damage from reactive oxygen species and other free radicals, resulting in cross-linkage or cleavage of proteins and lipoproteins, and oxidation of membrane lipids and lipoproteins. Damage to the cell membrane can result in myriad changes including loss of cell permeability, increased intercellular ionic concentration, and decreased cellular capacity to excrete or detoxify waste products. As the intercellular ionic concentration of potassium increases, colloid density increases and m-RNA and protein synthesis are hampered, resulting in decreased cellular repair. Some cells become so dehydrated they cannot function at all.
In aging, the regularity of tissue structure is lost, and individual cells enlarge, but the total number of cells decreases approximately 30%. Intercellular collagen and elastin increases. The proportion of soluble collagen decreases, and there may be increased crosslinking between long-chain collagen macromolecules. Elastin loses its discrete structure and elasticity and has an increased calcium content.
Sunlight exposure wreaks far greater destruction on the skin than time itself, and intensifies and augments the aging process. Free radical damage to the surface of the skin from sun exposure is manifested as lines, mottling, discoloration, precancers and cancers. Aging of both skin and other tissues is, in part, the result of constant free radical damage to cell membranes, leading to decreased cell function. This results in accumulation of waste products in the cells, such as lipofuscin; increase in the potassium content of the cells, which results in dehydration of the cells; and decreased production of messenger RNA and proteins.
The combination of sagging subcutaneous muscles and aging skin contributes to the overall cosmetic changes typically observed in aging, such as wrinkling, which involves the transition of a formerly smooth skin surface to one that appears unevenly shrunk and/or contracted, and the effects of gravity on the aging skin overlying the muscle tissue. It would be desirable to reverse or diminish these effects without cosmetic surgery, and to treat other conditions exhibiting sagging facial muscles such as myasthenia gravis.